Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

3028PHM Human Pharm II > Cancer biology and Chemotherapy > Flashcards

Cancer biology and Chemotherapy Flashcards

1
Q

Summarise the common adverse effect of myelosuppression seen with chemotherapy

A

Myelosupression occurs in chemo and refers to suppress of bone cells, mainly RBC and WBC

Suppression/destruction of RBC = will cause anaemia and severe fatigue

Suppression/destruction of WBC = weaken the immune system, inc the risk of infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

What chemo drug is known for causing cardiac toxicity?

A

Doxorubicin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What chemo drug is known for causing renal toxicity?

A

Cisplatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What chemo drug is known for causing pulmonary toxicity?

A

bleomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What chemo drug is known for causing neurotoxicity?

A

Vincristine

Paclitaxel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the cancer drugs that are DNA synthesis inhibitors

A

Folate antagonists = methotrexate, pemetrexed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the MOA of methotrexate?

A

Inhibit DNA synthesis due to inhibition of dihydrofolate –> prevent conversion to tetrahydropholate –> prevent IMP formation and thus no DNA synth

Reduce toxicity with folinic acid supplementation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the MOA of Pemetrexed?

A

Inhibit DHFR, tymidylate synthase and glycinamide ribonucleotide formyltransferase (GRAFT) –> prevents DNA synth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why are DNA synthesis inhibitor chemo drugs delivered intrathecally?

A

Do not penetrate CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What unique cancer can methotrexate be used in?

A

Trophoblastic tumours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are some notable ADRs of DNA synthesis inhibitor chemo drugs?

A

Myelosuppression = think WBC and RBC

Stomatitis and renal tox (methotrexate)

Hepatotox

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List the purine analogue chemo drugs

A

Mecaptopurine = hypoxanthine analogue

Thioguanine = guanine analogue

Used in blood cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the MOA of purine analogue chemo drugs?

A

Interfere with DNA synthesis due to inhibition of the biosynthesis of adenine and guanine

Prevent creation of functioning base pairs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are some notable ADRs with purine anaologues?

A

thioguanine = produces dose limiting myelosuppression

Mercaptopurine = causes hepatotoxicity

Both drugs contribute to secondary cancer formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

List the halogenated purine analogues used in chemo

A

FLudarabine

Cladribine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the MOA of halogenated purine analogue chemo drugs?

A

Pretend to be DNA

Incorporated into nascent DNA –> cause DNA chain termination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What unique cancer does cladribine treat?

A

hairy cell leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What types of cancers are commonly treated with fludarabine?

A

blood cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

List the relevant pyrimidine antagonist drugs used in cancer treatment

A

Cytarabine (cytosine arabinoside) = composed of cytosine and arabinose sugar
- Iv or Subcut

Fluorouracil = analogue of thymine
- IV = solid cancers
- Topical = non-invasive skin cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the MOA of cytarabine?

A

Active metabolites of cytarabine block DNA synthesis

- inhibition of DNA polymerase 
- Incorporation of drug into nascent DNA --> cause DNA chain termination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the MOA of fluorouracil?

A

Has two active metabolites:

- 5-fluorodeoxyuridine monophosphate (5-FdUMP) --> inhibit thymidylate synthetase --> prevent DNA building block thymidine synthesis 

- 5-fluorodeoxyuridine triphosphate (5-FdUTP) ---> incorporated into RNA by RNA polymerase --> interfere with RNA function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What genetic material does 5-FdUMP target?

A

DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What genetic material does 5-FdUTP target?

A

RNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe the rationale behind the combination of fluorouracil and leucovorin

A

Synergism happens

Allows 5-FdUMP to bind to thymidylate synthase more efficiently –> inc the ability to drop thymidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
What route of administration causes greatest myelosuppression w/ fluorouracil?
More problematic after bolus injection (push-injection) Mucosal damage is dose limiting with continuous infusion
25
What is the name of the pyrimidine antagonist which is a cell cycle specific drug?
Gemcitabine --> used as first line in pancreatic cancers
26
What is the MOA of gemcitabine?
gemcitabine --> converted to gemcitabine diphosphate and triphosphate --> inhibiting DNA synthesis in the S-phase
27
List the sub-class of DNA alkylating drugs and the relevant drugs within this (sub)-class
Subclass = nitrogen mustards cyclophosphamide Ifosfamide Chlorambucil
28
Generally explain the MOA of DNA Alkylating drugs
Cross-linking DNA strands by forming covalent bonds between alkyl groups of the drug and guanine bases of DNA ---> preventing uncoiling of the DNA
29
When is nausea worse with cyclophosphamide?
mild with orally Severe when given IV
30
What are some notable ADRs of DNA alkylating drugs?
Haemorrhagic cystitis = due to depletion of thiol groups Cyclophosphamide = dose-limiting myelosuppression
31
What is the MOA of Platinum compounds used in cancer treatment?
Form intrastrand and interstrand covalent bonds with DNA bases --> cross-link DNA
32
What can be used to counter the haemorrhagic cystitis seen predominantly with cyclophosphamide?
Administer mesna --> replenish thiol groups and prevent haemorrhagic cystitis
33
What are some notable ADRs of platinum compounds?
mild myelosuppression Severe nausea Nephrotoxicity Vomiting
34
What is mitomycin C and what is its MOA?
Antineoplastic abs MOA = alkylates DNA --> strand breakage --> inhibition of DNA synthesis
35
What is mitomycin commonly used for
Used along vincristine as salvage therapy for breast cancer
36
List the relevant DNA intercalating drugs
Anthracycline = Daunorubicin, Doxorubicin bleomycin dactinomycin
37
What are the MOAs of DNA intercalating drugs?
1) intercalation of DNA --> inserts self between DNA strands --> prevents DNA synthesis 2) Inhibits topoisomerase (I, II) --> allows DNA to break during replication --> impaired DNA synthesis 3) Formation of free radicals *Not absorbed into CNS
38
What are some notable ADRs of DNA intercalating drugs?
Dose limiting = myelosuppression and cardiac damage mucosal ulceration, tumour lysis syndrome IV = severe localised ulceration and necrosis
39
What is the relationship between PEG liposomal doxorubicin and cardiac toxicity?
Normally = Doxorubicin accumulates in cardiomyocytes --> inc ROS in the mitocondria --> cardiac toxicity --> dec LVEF PEG liposomal doxorubicin allows for more tissue specific targeting of doxorubicin into cancerous tissues --> more drug will enter cancer cells --> less drug entering healthy cells --> dec in cardiotoxic effects --> lesser impact on LVEF
40
What is the MOA of bleomycin?
Causes DNA intercalation during the G2 phase of cell replication Also causes iron-catalysed free radical formation and DNA strand breakage
41
What are some notable ADRs of bleomycin?
Pulmonary = interstitial fibrosis, hypoxia, death Mucocutaneous reactions = lack of aminohydralase in skin --> unable to breakdown drug --> drug accumulates in skin (mild stomatitis, skin hyperpigmentation, erythema
42
List the relevant mitotic inhibitor chemo drugs
Vinca alkaloids = vincristine, vinblastine IV only, neither enter CNS Taxanes = paclitaxel and docetaxel
43
What is the MOA of the Vinca Alkaloids?
Inhibit the assembly of microtubules --> prevent cell division and tumour growth
44
What are some notable ADRs of vinca alkaloids?
Vincristine = dose-limiting neurotox --> peripheral neuropathy (suppression of deep tendon reflexes, parethesias - hoarseness in voice, facial palsies, jaw pain Vinblastine = myelosuppression (dose-limiting) --> little neurotoxicity
45
What is the MOA of taxanes?
Block microtubule disassembly --> prevent replication/synthesis of new cells
46
What types of cancers do paclitaxel and docetaxel treat?
Docetaxel = castrate resistance prostate cancer (hormone independent cancer) Paclitxel =metastatic ovarian and breast cancer
47
What are some notable ADRs of taxanes?
dose-limiting myelosuppression Hypersensitivity reactions --> solubility issues
48
What is the function of topoisomerase I and II?
Topoisomerase I = breaks and reseals single stranded DNA Topoisomerase II = breaks and reseals in double-stranded DNA
49
Generally, what do topoisomerase inhibitors do?
Cause permanent strand breaks by inhibiting the resealing of nicked strands of DNA
50
List the relevant topoisomerase inhibitors and its MOA
Podophyllotoxins (etoposide) = inhibit topoisomerase II Camptothecin = inhibit topoisomerase I MOA = inhibition of both topoisomerase -> causing DNA/RNA damage --> prevent further replication --> DNA and cell synthesis
51
What class of drugs do topoisomerase inhibitors have a synergistic relationship with?
platinum compounds
52
List the relevant topoisomerase inhibitors
Camptothecin analogues = irinotecan (biliary excretion) and topotecan (renal excretion) Podphyllotoxins = etoposide
53
How is irinotecan metabolised?
Rapidly metabolised to active metabolite called SN-38 --> greater anti-tumour activity SN-38 excreted primarily by bile
54
What is irinotecan commonly used to treat?
colorectal cancer that has recurred or progressed following fluorouracil therapy
55
What are some notable ADRs of camptothecin analogues?
Both topotecan and irinotecan = dose limiting myelosuppression Irinotecan produces diarrhoea
56
List the relevant targeted drugs that inhibit protein kinases
Imatinib Dasatinib Nilotinib
57
What is the MOA of protein kinase inhibitor (imatinib) targeted drugs?
Inhibit BCR-ABL tyrosine kinase --> inhibit serine-threonine kinase --> dec malignant transformation and proliferation and inc apoptosis
58
Which protein kinase inhibitors target EGFR?
Erlotinib
59
What is the MOA of erlotinib?
Protein kinase inhibitor that inhibits EGFR Dec cell proliferation, inc apoptosis, dec invasion and metastasis, dec angiogenesis Causing inc cell destruction, slowing cancer cell proliferation Cetuximab, panitumumab = have same MOA
60
What is the MOA of venetoclax?
Inhibit BCL-2 --> promotes apoptosis --> activates caspases --> cancer cell death
61
What is the MOA of sunitinib?
Inhibits VEGFR --> inhibits angiogenesis Bevacizumab works the same
62
What is the MOA of rituximab?
Binds CD20 antigen on non-Hodgkin lymphoma cancer --> reduce/impair early cell cycle initiation
63
What is the MOA of trastuzumab?
recombinant human mab binds to epidermal growth factor-2 (HER2/neu)[tyrosine kinase] --> inhibit cell proliferation
64
What is the MOA of Ipilimumab?
Antibody that binds CTLA-4 --> preventing release of T cell inhibitory signalling --> T cell activation
65
What are some notable ADRs of ipilimumab (yervoy)?
Severe/fatal immune mediated ADR = stop drug indefinitely and commence on high dose corticosteroid therapy Colitis Hepatitis Dermatitis Neuropathies
66
What is the MOA of pembrolizumab? ADRs?
mab --> bind PD-1 receptor --> block interaction between PD-1 and ligands (PD-L1 and PD-L2) ADR = colitis, pneumonitis, hepatitis, hypophysitis --> stop tx
67
What is the MOA of abemaciclib?
CDK 4/6 inhibitor --> interfere w/ cell cycle progression --> halt cancer progression of Her+ve/Her2-ve breast cancer
68
What is the MOA and ADR of trodelvy?
Sacituzumab govitecan-hziy Trop2-directed antibody and topoisomerase inhibitor conjugate ADR = Neutropenia, diarrhoea, N/V Inc ADR risk w/ reduced UGT1A1 activity
69
What is the role of tamoxifen in cancer treatment?
Oestrogen antagonist on breasts --> allow shrinkage of tumour
70
What is the role of aromatase inhibitors (anastrazole and letrozole) in cancer treatment?
Prevent oestrogen synth --> useful in hormone dependent breast cancer
71
What is an example of a GnRH agonist? What is the MOA of this group?
Leuprorelin MOA = inc GnRH stimulation which acts on the pituitary --> inc LH on testes --> inc testosterone release --> excessive hormone production --> negative feedback loop of hypothalamus and pituitary --> eventual dec in tumour size/growth due to dec testosterone
72
What is an example of a GnRH antagonist? What is the MOA of this group?
Degarelix MOA = Inhibit GnRH --> inhibits release of LH --> no LH effect on testes ---> dec testosterone production --> less testosterone action on testes --> hormone sensitive prostate cancer dec
73
What is an example of an androgen antagonist? What is the MOA of this group?
Flutamide, bicalutamide MOA = prevent the action of dihydrotestosterone by competitively binding to the androgen receptor and inhibiting the binding of DHT ---> inhibition of cell proliferation/DNA replication due to lack of testosterone
74
What is the MOA of ketoconazole and abiraterone in prostate cancer?
1) inhibit biosynthesis of testosterone 2) Inhibit androstenedione (has role in synth of oestrogen and testosterone) and DHEA DHEAs --> inhibit testosterone release --> reduced cell proliferation
75
What is an example of 5alpha-reductase inhibitor? What is the MOA of this group?
Finasteride, dutasteride MOA = inhibit the conversion of testosterone to potent dihydrotestosterone --> slows growth of testosterone dependent prostate cancers
76
What are some ADRs of androgen-deprivation therapy?
Sexual = genital shrinkage, erectile dysfunction, libido loss Physical = weight gain, gyno, muscle atrophy Metabolic = osteoporosis, anaemia, HTN, heart disease, diabetes Emotional/cognitive Systemic = fatigue TUmour "flare" = GnRH agonist --> tumour will worsen initally like GnRH agonist --> tumour will shrink/sx improve
77
Explain the direct action of radiotherapy
Ionised radiation --> DNA damage --> cells apoptose and die
78
Explain the indirect damage of radiotherapy
Ionised radiation --> inc free radical production --> DNA damage --> inc cytokine production --> cell death

3028PHM Human Pharm II (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions